Drosophila ClC-a is required in glia of the stem cell niche for proper neurogenesis and wiring of neural circuits

果蝇 ClC-a 是干细胞微环境胶质细胞中必要的成分,可确保神经发生和神经回路正确连接

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作者:Haritz Plazaola-Sasieta, Qi Zhu, Héctor Gaitán-Peñas, Martín Rios, Raúl Estévez, Marta Morey

Abstract

Glial cells form part of the neural stem cell niche and express a wide variety of ion channels; however, the contribution of these channels to nervous system development is poorly understood. We explored the function of the Drosophila ClC-a chloride channel, since its mammalian ortholog CLCN2 is expressed in glial cells, and defective channel function results in leukodystrophies, which in humans are accompanied by cognitive impairment. We found that ClC-a was expressed in the niche in cortex glia, which are closely associated with neurogenic tissues. Characterization of loss-of-function ClC-a mutants revealed that these animals had smaller brains and widespread wiring defects. We showed that ClC-a is required in cortex glia for neurogenesis in neuroepithelia and neuroblasts, and identified defects in a neuroblast lineage that generates guidepost glial cells essential for photoreceptor axon guidance. We propose that glia-mediated ionic homeostasis could nonautonomously affect neurogenesis, and consequently, the correct assembly of neural circuits.

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